To the Editor: We read with interest the article by Cezard et al (1) entitled “A Prospective Study of the Efficacy and Tolerance of a Chimeric Antibody to Tumor Necrosis Factors in Severe Pediatric Crohn’s Disease”.
Chimeric Antibody to Tumor Necrosis Factors (Remicade) in Severe Pediatric Crohn’s Disease.” The authors suggested that prolonged systematic re-treatment with infliximab should be considered because of the short duration of beneficial effects of this drug.
We report our experience of 10 patients with Crohn’s Disease treated with periodic infliximab infusion: five patients due to corticosteroid-dependent intestinal disease and five patients due to lack of response to conventional medical therapy. Every patient in our series received infliximab (5 mg/kg) by intravenous infusion after a premedication with antihistaminic and steroids. The second infusions were administered after 4 weeks, and subsequent infusions were administered every 8 weeks to maintain the clinical remission according to clinical trials in adult patients (2).
During the period reviewed (2000–2003), the 10 patients received a total of 97 drug infusions, with a median of 8 infusions (range, 2–20). In our study, three patients had severe anaphylactic reaction (two patients at the second infusion and one patient at the third) and the treatment was terminated (3,4). For this reason, only 7 of the 10 patients continued the treatment; in these patients we could evaluate the efficacy of the Infliximab in maintaining the remission. In this group, Infliximab induced remission in five cases after the first infusion; two patients obtained only a partial remission and the treatment was suspended, after 7 and 11 infusions, respectively, because they developed a mild stenosis with subocclusion during the treatment. The five responsive patients continued the periodic infliximab infusions (with a total of 50 infusions, range 6–20). Four patients maintained the remission and are still in follow-up.
In our work, as in other studies (1,5–9), it was observed that the steroids were suspended in three patients and gradually diminished in two patients during follow-up. In one of the five patients in follow-up, the treatment was suspended due to a constant increase of the pCDAI after the sixteenth infusion and radiologic evidence of ascending colon stenosis. In our experience infliximab therapy had a favourable effect on patient outcomes and, as in other studies (1,5–9), permitted us to suspend steroids in three patients and gradually decrease them in two patients. Regarding the efficacy of infliximab in maintaining clinical remission, we observed that this drug was able to maintain clinical remission mainly in patients who showed an early remission with this treatment.
Nonetheless, the prolonged use of the drug does not prevent an evolution towards stenosis observed in three of the seven patients in periodic treatment. One of these three patients was homozygous carrier of NOD2/CARD15 mutation.
Despite the small number of patients studied, we consider our experience original because it shows that the prolonged systematic infliximab therapy in pediatric patients, up to now reported only in clinical trials for adult patients, seems not able to prevent intestinal stenosis.
Bambino Gesù Children’s Hospital, Rome, Italy
1. Cezard JP, Nouaili N, Talbotec C, et al. A prospective study of the efficacy and tolerance of a chimeric antibody to tumor necrosis factors (Remicade) in severe pediatric Crohn’s disease. J Ped Gastroenterol Nutr
2. Diamanti A, Castro M, Papadatou B, Ferretti F, Gambarara M, Ferretti F. Severe anaphylactic reaction to infliximab in padiatric patients with Crohn’s disease. J Pediatr
3. Diamanti A, Papadatou B, Knafelz D, Gambarara M, Ferretti F, Castro M. Complications of infliximab Therapy in children and adolescents affected by Crohn’s disease. Am J Gastroenterol
4. Hanauer SB, Feagan BG, Lichtenstein GR, et al. ACCENT I Study Group. Maintenance infliximab for Crohn’s disease: the ACCENT 1 randomised trial. Lancet
5. Hyams JS, Markowitz J, Wyllie R. Use of Infliximab in the treatment of Crohn’s disease in children and adolescents. J Pediatr
6. Kugathasan S, Werlin SL, Martinez A, Rivera MT, Heikenen JB, Binion DG. Prolonged duration of response to Infliximab in early but not late pediatric Crohn’s disease. Am J Gastroenterol
7. Serrano MS, Schmidt-Sommerfeld E, Kilbaugh TJ, Brown RF, Udall JN, Mannick EE. Use of Infliximab in pediatric patients with inflammatory bowel disease. Ann Pharmacother
8. Stephens MC, Shepanski MA, Mamula P, Markowitz JE, Brown KA, Baldassano R. Safety and steroid- sparing experience using infliximab for Crohn’s disease at a pediatric inflammatory bowel disease center. Am J Gastroenterol
9. Lionetti P, Bronzini F, Salvestrini C, et al. Response to infliximab is related to disease duration in paediatric Crohn’s disease. Aliment Pharmacol Ther